Disease relevance of Ndst1

• The NDST-1 null mice developed respiratory distress and atelectasis that subsequently caused neonatal death [1].

High impact information on Ndst1

• We show that properly synthesized heparan sulfate is required for the normal development of the brain and face, and that Ndst1 is a modifier of heparan sulfate-dependent growth factor/morphogen signalling in those tissues [2].
• Mutant mice bearing a targeted disruption of the heparan sulfate (HS) modifying enzyme GlcNAc N-deacetylase/N-sulfotransferase 1 (Ndst1) exhibit severe developmental defects of the forebrain and forebrain-derived structures, including cerebral hypoplasia, lack of olfactory bulbs, eye defects and axon guidance errors [2].
• Heparan sulfate synthesized by mouse embryonic stem cells deficient in NDST1 and NDST2 is 6-O-sulfated but contains no N-sulfate groups [3].
• All these modifications are believed to depend on initial glucosamine N-sulfation carried out by the enzyme glucosaminyl N-deacetylase/N-sulfotransferase (NDST) [3].
• In vitro translation of a reporter gene located downstream of the UTRs demonstrated the presence of internal ribosome entry sites, providing an additional, cap-independent step in fine-tuning NDST expression [4].

Biological context of Ndst1

• Here, we report on the effects of NDST deficiency on Ca2+ kinetics in myotubes from NDST-1- and NDST-2-deficient mice, indicating a novel role for heparan sulfate in skeletal muscle physiology [5].

Anatomical context of Ndst1

• Biochemical analysis of heparan sulfate purified from fibroblast cultures, lung, and liver of NDST-1-deficient embryos demonstrated a dramatic reduction in N-sulfate content [6].
• We here report that targeted gene disruption of NDST-1 in the mouse results in a structural alteration of heparan sulfate in most basement membranes as revealed by immunohistochemical staining of fetal tissue sections using antibodies raised against heparan sulfate [6].
• Immunostaining for specific heparan sulfate epitopes showed major changes in the heparan sulfate composition in skeletal muscle tissue derived from NDST-1-/- mice and NDST-/- cultured myotubes [5].
• NDST-1 knockout mice with altered HS structure die at birth due to lung failure, whereas lack of NDST-2 results in abnormal mast cells [7].

Associations of Ndst1 with chemical compounds

• Cerebral hypoplasia and craniofacial defects in mice lacking heparan sulfate Ndst1 gene function [2].
• Glucosaminyl N-deacetylase/N-sulfotransferase (NDST) catalyzes the first modifying step in the biosynthesis of the polysaccharide [6].
• The initial modification of the precursor polysaccharide, N-deacetylation followed by N-sulfation of selected N-acetyl-D-glucosamine residues, is catalyzed by the enzyme glucosaminyl N-deacetylase/N-sulfotransferase (NDST) [5].

References